期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 9, 期 6, 页码 1639-1647出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0968-0896(01)00059-1
关键词
-
The novel amide linked Angiotensin II(ANG II) cyclic analogue cyclo(3, 5) -[Sar(1)-Lys(3)-Glu(5)-Ile(8)] ANG II (18) has been designed, synthesized and bioassayed in anesthetized rabbits. The constrained cyclic analogue with a lactam amide bridge linking a Lys-Glu pair at positions 3 and 5 and possessing Ile at position 8, was synthesized by solution procedure using the maximum protection strategy. This analogue was found to be inhibitor of Angiotensin II. NMR spectroscopy coupled with computational analysis showed clustering between the side chains of the key aminoacids Tyr(4)-His(6)-Ile(8) Similar to that observed with ANG II. The obtained data show that only pi*-pi* interactions observed in ANG II or its superagonist Sar(1) [ANG II] are missing. Therefore, it can be concluded that these interactions are essential for agonist activity. Conformational analysis comparisons between ATI antagonists losartan, eprosartan and irbesartan with C-terminal segment of cyclic compound 18 revealed structural similarities. (C) 2001 Elsevier Science Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据